Life Cycle Of Virus (Replication)
The genome of the rhabdovirus is a single linear molecule of minus sense ssRNA, 11-12 kb in size. It encodes for five major proteins:
N = structural nucleoprotein NS = phosphoprotein, binds promoter sequence and L gene M = matrix protein G = glycoprotein peplomer (site for Ab binding) L = transcriptase, 5'-cap methylase, 3'polyA polymerase, and protein kinase. The virus particle initiates it's replication cycle by the binding of its G protein spikes to receptors of the host cell surface. Reference:-http://webspace.ship.edu/lhelli/rabies/ |
Cycle Of Infection And Replication
- Adsorption (receptors and virion interation).
- Penetration (virus entry).
- Uncoating (envelope removal).
- Transcription (synthesis of mRNAs).
- Translation (Synthesis of structural proteins).
- Processing (G-protein gycosylation).
- Replication (production of genomic RNA from intermediate strand.
- Assembly.
- Budding (complete virions).
A viral-encoded polymerase (L gene) transcribes the genomic strand of rabies RNA into leader RNA and five capped and polyadenylated mRNAs, which are translated into proteins. Translation, which involves the synthesis of the N, P, M, G and L proteins, occurs on free ribosomes in the cytoplasm. Although G protein synthesis is initiated on free ribosomes, completion of synthesis and glycosylation (processing of the glycoprotein), occurs in the endoplamsic reticulum (ER) and Golgi apparatus. The intracellular ratio of leader RNA to N protein regulates the switch from transcription to replication. When this switch is activated, replication of the viral genome begins. The first step in viral replication is synthesis of full-length copies (postive strands) of the viral genome. When the switch to replication occurs, RNA transcription becomes "non-stop" and stop codons are ignored. The viral polymerase enters a single site on the 3’ end of the genome, and proceeds to synthesize full-length copies of the genome. These positive strands of rabies RNA serve as templates for synthesis of full-length negative strands of the viral genome.
During the assembly process, the N-P-L complex encapsulates negative-stranded genomic RNA to form the RNP core, and the M protein forms a capsule, or matrix, around the RNP. The RNP-M complex migrates to an area of the plasma membrane containing glycoprotein inserts, and the M-protein initiates coiling. The M-RNP complex binds with the glycoprotein, and the completed virus buds from the plasma membrane. Within the central nervous system (CNS), there is preferential viral budding from plasma membranes. Conversely, virus in the salivary glands buds primarily from the cell membrane into the acinar lumen. Viral budding into the salivary gland and virus-induced aggressive biting-behavior in the host animal maximize chances of viral infection of a new host.
When a human or animal is injected with infected saliva, the rabies virus replicates at the site of inoculation. Aided by the G protein, the viral envelope attaches and fuses with the host cell membrane. Invagination of the plasma membrane with clathrin-coated pits allows cytoplasmic absorption via pinocytosis. The virions aggregate with the large endosomes, and after fusion with their membranes, they initiate the uncoating and release of the viral RNP into the cytoplasm. Since the rabies virus has a linear –ssRNA genome, messenger RNAs are produced to permit virus replication using the host cell machinery. In particular, translation of the genome occurs on the free ribosomes in the cytoplasm, and some posttranslational processing occurs in the endoplasmic reticulum and Golgi apparatus.
Reference:-http://en.wikipedia.org/wiki/Rabies_virus
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